ArticleThe Journal of experimental medicine2015
DNAM-1 controls NK cell activation via an ITT-like motif.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 133 citations in OpenAlex.
- Intercellular Transfer of CD155 Mediated by Melanoma Extracellular Vesicles Downregulates DNAM-1 Expression on NK Cells.International journal of molecular sciences · 2026Article
- LFA-1 mechanical dose controls DNAM-1 signalling and perforin polarization in NK cells.RSC advances · 2026Article
- CD155 and its receptors in glioma: prospects for emerging immune checkpoint inhibitors.Acta neuropathologica communications · 2026Review
- Establishment and characterization of NKMS-1, a novel mouse NK cell line.Scientific reports · 2026Article
- DNAM-1 mediates NK-cell activation and host-pathogen interaction via direct binding to fungal cell wall proteases.Communications biology · 2026Article
- Interaction of CD99 and its ligands regulates immunoregulatory pathways in NK cells.Frontiers in immunology · 2026Article
- The PVR-TIGIT/CD96/CD226 axis: a novel immune checkpoint target in ovarian cancer.Frontiers in immunology · 2026Review
- Immunotherapeutic strategies targeting the PVR-TIGIT/CD96/CD226 signaling pathway in glioma treatment.Annals of medicine · 2025Review
- Kaempferol regulating macrophage foaming and atherosclerosis through Piezo1-mediated MAPK/NF-κB and Nrf2/HO-1 signaling pathway.Journal of advanced research · 2025Article
- The Immune Regulatory Functions of CD226 and Its Implications in Immune-Mediated Diseases.Biomolecules · 2025Review
- CD155 blockade enhances allogeneic natural killer cell-mediated antitumor response against osteosarcoma.Journal for immunotherapy of cancer · 2025Article
- A chimeric antigen receptor tailored to integrate complementary activation signals potentiates the antitumor activity of NK cells.Journal of experimental & clinical cancer research : CR · 2025Article
- Inhibition of CD226 co-stimulation suppresses diabetes development in the NOD mouse by augmenting regulatory T cells and diminishing effector T cell function.Diabetologia · 2025Article
- Spatial and Single-Cell Analyses Reveal Heterogeneity of DNAM-1 Receptor-Ligand Interactions That Instructs Intratumoral γδT-cell Activity.Cancer research · 2025Article
- NKG2D triggering hampers DNAM-1-mediated signaling in human NK cells.Frontiers in immunology · 2025Article
- Blockade of CD155 and CD276 by Monoclonal Antibodies Fosters Immune Tolerance and Promotes Stable Engraftment of iPSC-Derived Islets in Allogeneic Humanized Mice.Transplant international : official journal of the European Society for Organ Transplantation · 2025Article
- Comprehensive snapshots of natural killer cells functions, signaling, molecular mechanisms and clinical utilization.Signal transduction and targeted therapy · 2024Review
- Revisiting T-cell adhesion molecules as potential targets for cancer immunotherapy: CD226 and CD2.Experimental & molecular medicine · 2024Review
- NK Receptor Signaling Lowers TCR Activation Threshold, Enhancing Selective Recognition of Cancer Cells by TAA-Specific CTLs.Cancer immunology research · 2024Article
- CD226 implicated in Akt-dependent apoptosis of CD4Cell death & disease · 2024Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
DNAM-1 (CD226) is an activating receptor expressed on natural killer (NK) cells, CD8(+) T cells, and other immune cells. Upon recognition of its ligands, CD155 and CD112, DNAM-1 promotes NK cell-mediated elimination of transformed and virus-infected cells. It also has a key role in expansion and maintenance of virus-specific memory NK cells. Herein, the mechanism by which DNAM-1 controls NK cell-mediated cytotoxicity and cytokine production was elucidated. Cytotoxicity and cytokine production triggered by DNAM-1 were mediated via a conserved tyrosine- and asparagine-based motif in the cytoplasmic domain of DNAM-1. Upon phosphorylation by Src kinases, this motif enabled binding of DNAM-1 to adaptor Grb2, leading to activation of enzymes Vav-1, phosphatidylinositol 3' kinase, and phospholipase C-γ1. It also promoted activation of kinases Erk and Akt, and calcium fluxes. Although, as reported, DNAM-1 promoted adhesion, this function was signal-independent and insufficient to promote cytotoxicity. DNAM-1 signaling was also required to enhance cytotoxicity, by increasing actin polymerization and granule polarization. We propose that DNAM-1 promotes NK cell activation via an immunoreceptor tyrosine tail (ITT)-like motif coupling DNAM-1 to Grb2 and other downstream effectors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.